Insulin secretion was studied in male GRC Wistar rats 6 and 24 mo of age in order to evaluate whether renal failure and hyperparathyroidism frequently observed in senescent male rats plays a role in age-associated reduction in insulin secretion. Senescent rats with chronic renal failure and high PTH exhibited markedly reduced levels of initial phase and total glucose-stimulated insulin secretion from isolated pancreatic islets compared to normal 6 mo adult rats. Insulin secretion from islets from senescent rats with normal renal function and PTH levels was similar to that observed in 6 mo adult rats. The significance of the project lies in the demonstration that impaired insulin secretion by pancreatic islets of senescent rats is not related to age per se, but is associated with chronic renal failure and secondary hyperparathyroidism that develop in many but not all old animals. The results indicate that studies examining the effect of aging on organ function should take into consideration the level of renal function and of serum PTH, since both chronic renal failure and excess PTH are known to adversely affect the functional integrity of many organs.